Iontophoresis is the application of an electrical current to transport ions through intact skin. One particularly advantageous application of iontophoresis is the non-invasive transdermal delivery of ionized drugs or other therapeutic agents into a patient. This is done by applying low levels of current to a patch placed on the patient's skin, which forces the ionized drugs contained in the patch through the patient's skin and into his or her bloodstream.
Passive transdermal patches, such as those used to deliver nitroglycerin for angina pectoris, estradiol for hormone replacement, and nicotine to stop smoking, can only use a limited number of drugs because they work by diffusion. Iontophoresis advantageously expands the range of drugs available for transdermal delivery, including, for example, parenteral drugs (e.g., peptides). Further, because the amount of drug delivered is related to the amount of current applied, the drug delivery rate can be precisely controlled by controlling the current, unlike the passive transdermal patches. This allows for more rapid delivery (onset) and drug reduction (offset) in the patient.
When compared to drug delivery by needle injection, iontophoresis is non-evasive. Also, iontophoresis avoids the risks and inconvenience associated with IV (intravenous) delivery. In addition, when compared to oral ingestion of drugs, drug delivery by iontophoresis bypasses the GI tract, thus reducing side-effects such as drug loss, indigestion and stomach distress, and eliminating the need for swallowing the drug. Iontophoresis also avoids drug loss due to hepatic first pass metabolism by the liver that occurs when drugs are ingested.
Further, transdermal drug delivery by iontophoresis permits continuous delivery of drugs with a short half life and easy termination of drug delivery. Because iontophoresis is more convenient, there is a greater likelihood of patient compliance in taking the drug. Thus, for all of the above reasons, iontophoresis offers an alternative and effective method of drug delivery, and an especially useful method for children, the bedridden and the elderly.
An iontophoretic drug delivery system typically includes a current source, such as a battery and current controller, and a patch. The patch includes an active reservoir and a return reservoir. The active reservoir contains the ionized drug. The return reservoir typically contains a saline gel and collects ions emanating from the patient's skin when the drug is being delivered into the patient's skin. The patch also has two electrodes, each arranged inside the active and return reservoirs to be in respective contact with the drug and saline. The anode (positive electrode) and the cathode (negative electrode) are respectively electrically connected to the anode and cathode of the current source by electrical conductors. Either the anode or the cathode is arranged within the drug reservoir, depending on the charge of the ionized drug, and is designated the active electrode. The other electrode is arranged within the return reservoir, and is designated the return electrode.
When current from the current source is supplied to the active electrode, the drug ions migrate from the drug reservoir toward and through the skin of the patient. At the same time, ions flow from the patient's skin into the saline solution of the return reservoir. Charge is transferred into the return electrode and back to the current source, completing the iontophoretic circuit.
The electronic controller between the battery and the patch controls the amount of current delivered to the patch. The controller may control the drug delivery profile by controlling the delivered current so that drug delivery to the patient is accomplished at a constant or varying rate, or over a short, long or periodic time interval. This type of controller may require relatively complex electrical circuitry to meet the above requirements.
Iontophoretic drug delivery circuits may be powered directly by a multi-celled battery. (These types of circuits, however, are not admitted to be prior art with respect to the present invention by their mention in this Background section.) This approach, however, has a number of drawbacks. Although any given voltage can be attained by connecting an appropriate number of cells in series, each additional cell increases the weight and size of the resulting package, and increases the cost of the device.
DC--DC inductive-type converters may be used to step up a supply voltage to eliminate the need for a large stack of battery cells. Inductive-type DC--DC converters, however, include inductive components such as transformers which are relatively bulky, expensive, and heavy, and emit electromagnetic noise.